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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 12 - 2024 | doi: 10.3389/fbioe.2024.1449955
This article is part of the Research Topic Advances in Biotechnological Approaches for Reproductive Tissue Engineering View all 6 articles

Engraftment of self-renewing endometrial epithelial organoids promotes endometrial regeneration by differentiating into functional glands in rats

Provisionally accepted
Xiaona LIN Xiaona LIN 1*Yana Ma Yana Ma 1*Jingjing Qian Jingjing Qian 1*Xin Xu Xin Xu 1*Cheng Wei Cheng Wei 1Minyuan Wang Minyuan Wang 1*Peipei Zhang Peipei Zhang 1*Sijia Chen Sijia Chen 1*Lingyan Zhang Lingyan Zhang 1*Yanling Zhang Yanling Zhang 1*Yanpeng Wang Yanpeng Wang 2Wenzhi Xu Wenzhi Xu 1Mengying Liu Mengying Liu 1*
  • 1 Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
  • 2 Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    Extensive trauma disrupts endometrial regeneration by diminishing endometrial stem or progenitor cells. Endometrial epithelial organoids (EEOs) are used for endometrial regeneration. However, how EEOs repair injured endometrial tissues and their advantages over bone marrow mesenchymal stem cells (BMSCs) are unclear. This study explored whether EEOs surpass BMSCs to repair injured endometrium and examined whether endometrial restoration involves integrating EEOs into the endometrial tissue of the recipient. Rat EEOs (rEEOs) mimicking the features of the rat endometrium were developed. An endometrial injury rat model was used to compare the effects of rEEOs and rat BMSCs (rBMSCs) on endometrial regeneration and reproductive recovery. Bulk RNAsequencing analysis was conducted to investigate the capacity of rEEOs for endometrial regeneration and identify discrepancies between rEEOs and rBMSCs. Green fluorescent protein (GFP)-labeled rEEOs or red fluorescent protein-labeled rBMSCs were transplanted to track the transplanted cells in vivo. Fertility recovery in rats transplanted with rEEOs was more comparable to that of normal rats than in rBMSC-treated rats. rEEOs had a high concentration of endometrial epithelial stem or progenitor cells and secreted vascular endothelial growth factor-A to promote endometrial neovascularization. Cells from GFP-labeled rEEOs integrated and differentiated into functional glands within the injured endometrium. Transplanting EEOs restored the morphology and function of severe endometrial injury better than BMSC transplantation. EEO cells repair the endometrium by differentiating into functional glandular epithelial cells. These findings offer preclinical evidence supporting in vitro expansion and transplanting of EEOs as promising approaches to restore fertility in women with insufficient endometrial regeneration.

    Keywords: endometrial regeneration, 3D-culture, endometrial epithelial organoids, Bone marrow mesenchymal stem cells, Transplantation, Infertility

    Received: 16 Jun 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 LIN, Ma, Qian, Xu, Wei, Wang, Zhang, Chen, Zhang, Zhang, Wang, Xu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xiaona LIN, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
    Yana Ma, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
    Jingjing Qian, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
    Xin Xu, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
    Minyuan Wang, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
    Peipei Zhang, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
    Sijia Chen, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
    Lingyan Zhang, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
    Yanling Zhang, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China
    Mengying Liu, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Hangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.